Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells

Oncogene volume 21, pages 6132–6137 (2002)Cite this article

Abstract

Death induced by doxorubicin (dox) in neuroblastoma (NB) cells was originally thought to occur via the Fas pathway, however since studies suggest that caspase-8 expression is silenced in most high stage NB tumors, it is more probable that dox-induced death occurs via a different mechanism. Caspase-8 silenced N-type invasive NB cell lines LAN-1 and IMR-32 were investigated for their sensitivity to dox, and compared to S-type noninvasive SH-EP NB cells expressing caspase-8. All cell lines had similar sensitivities to dox, independently of caspase-8 expression. Dox induced caspase-3, -7, -8 and -9 and Bid cleavage in S-type cells and death was blocked by caspase inhibitors but not by oxygen radical scavenger BHA. In contrast, dox-induced death in N-type cells was caspase-independent and was inhibited by BHA. Dox induced a drop in mitochondrial membrane permeability in all cell lines. Dox-induced death in S-type cells gave rise to apoptotic nuclei, whereas in N-type cells nuclei were non-apoptotic in morphology. Transfection of SH-EP cells with a dominant negative FADD mutant inhibited TRAIL-induced death, but had no effect on dox-induced apoptosis. These results suggest that S-type cells undergo apoptosis after dox treatment independently of death receptors, whereas N-type cells are killed by a caspase-independent mechanism.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Bian X, McAllister-Lucas LM, Shao F, Schumacher KR, Feng Z, Porter AG, Castle VP, Opipari Jr AW . 2001 J. Biol. Chem. 276: 48921–48929

  • Daniel PT, Wieder T, Sturm I, Schulze-Osthoff K . 2001 Leukemia 15: 1022–1032

  • Ferreira CG, Span SW, Peters GJ, Kruyt FA, Giaccone G . 2000 Cancer Res. 60: 7133–7141

  • Fulda S, Meyer E, Friesen C, Susin SA, Kroemer G, Debatin KM . 2001 Oncogene 20: 1063–1075

  • Fulda S, Sieverts H, Friesen C, Herr I, Debatin KM . 1997 Cancer Res. 57: 3823–3829

  • Fulda S, Susin SA, Kroemer G, Debatin KM . 1998 Cancer Res. 58: 4453–4460

  • Goldman SC, Chen CY, Lansing TJ, Gilmer TM, Kastan MB . 1996 Am. J. Pathol. 148: 1381–1385

  • Green DR, Reed JC . 1998 Science 281: 1309–1312

  • Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J . 2000 Nat. Immunol. 1: 489–495

  • Hopkins-Donaldson S, Bodmer JL, Bourloud KB, Brognara CB, Tschopp J, Gross N . 2000 Cancer Res. 60: 4315–4319

  • Kataoka T, Schroter M, Hahne M, Schneider P, Irmler M, Thome M, Froelich CJ, Tschopp J . 1998 J. Immunol. 161: 3936–3942

  • La Quaglia MP, Manchester KM . 1996 J. Pediatr. Surg. 31: 315–318

  • Leist M, Jaattela M . 2001 Nat. Rev. Mol. Cell Biol. 2: 589–598

  • McCurrach ME, Connor TM, Knudson CM, Korsmeyer J, Lowe SW . 1997 Proc. Natl. Acad. Sci. USA 94: 2345–2349

  • McKenzie PP, Guichard SM, Middlemas DS, Ashmun RA, Danks MK, Harris LC . 1999 Clin. Cancer Res. 5: 4199–4207

  • Miyazaki K, Yoshida H, Sasaki M, Hara H, Kimura G, Mak TW, Nomoto K . 2001 J. Biochem. (Tokyo) 129: 963–969

  • Newton K, Strasser A . 2000 J. Exp. Med. 191: 195–200

  • Ostermeyer AG, Runko E, Winkfield B, Ahn B, Moll UM . 1996 Proc. Natl. Acad. Sci. USA 93: 15190–15194

  • Oue T, Fukuzawa M, Kusafuka T, Kohmoto Y, Imura K, Nagahara S, Okada A . 1996 J. Pediatr. Surg. 31: 251–257

  • Sartorius UA, Krammer PH . 2002 Int. J. Cancer 97: 584–592

  • Scaffidi C, Schmitz I, Zha J, Korsmeyer SJ, Krammer PH, Peter ME . 1999 J. Biol. Chem. 274: 22532–22538

  • Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang H-G, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ . 1999 J. Cell Biol. 144: 281–292

  • Spix C, Aareleid T, Stiller C, Magnani C, Kaatsch P, Michaelis J . 2001 Eur. J. Cancer 37: 722–729

  • Strasser A, O'Connor L, Dixit VM . 2000 Annu. Rev. Biochem. 69: 217–245

  • Susin SA, Daugas E, Ravagnan L, Samejima K, Zamzami N, Loeffler M, Costantini P, Ferri KF, Irinopoulou T, Prevost MC, Brothers G, Mak TW, Penninger J, Earnshaw WC, Kroemer G . 2000 J. Exp. Med. 192: 571–580

  • Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM, Kidd VJ . 2000 Nat. Med. 6: 529–535

  • Vercammen D, Brouckaert G, Denecker G, Van de CM, Declercq W, Fiers W, Vandenabeele P . 1998 J. Exp. Med. 188: 919–930

  • Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ . 2001 Science 292: 727–730

Download references

Acknowledgements

We would like to thank Professor Jürg Tschopp, Institute of Biochemistry, Lausanne, Switzerland for his kind gift of the vector encoding FADD-DN. This work was funded by Oncosuisse SLF605-1-1998, Foundation FORCE and the Emma Muschamp Foundation.

Author information

Authors and Affiliations

  1. Department of Pediatric Onco-Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, CH1011, Switzerland

    Sally Hopkins-Donaldson, Pu Yan, Katia Balmas Bourloud, Annick Muhlethaler & Nicole Gross

  2. Institute of Biochemistry, University of Lausanne, Epalinges, CH-1066, Switzerland

    Jean-Luc Bodmer

Authors
  1. Sally Hopkins-Donaldson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pu Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katia Balmas Bourloud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annick Muhlethaler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean-Luc Bodmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicole Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicole Gross.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hopkins-Donaldson, S., Yan, P., Bourloud, K. et al. Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. Oncogene 21, 6132–6137 (2002). https://doi.org/10.1038/sj.onc.1205879

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205879

Keywords

This article is cited by

Search

Advanced search

Quick links